Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment

Mol Neurobiol. 2021 Sep;58(9):4425-4436. doi: 10.1007/s12035-021-02393-y. Epub 2021 May 22.

Abstract

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.

Keywords: Ganciclovir; Gene therapy; Glioblastoma multiform; Iran; Mesenchymal stem cell; Suicidal gene.

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Drug Delivery Systems
  • Feasibility Studies
  • Female
  • Ganciclovir / administration & dosage*
  • Ganciclovir / therapeutic use
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • HEK293 Cells
  • Humans
  • Male
  • Mesenchymal Stem Cells*
  • Middle Aged
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Ganciclovir